Pathophysiology and novel drug development targeting deafness-associated potassium channel KCNQ4

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18802
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Shinshu University
• Principal Investigator: Timothy Day 信州大学, 医学部, 研究員 (00838667)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 難聴 / 遺伝子 / モデルマウス

Outline of Final Research Achievements

We have completed experimental testing for data in the project titled “Pathophysiology and novel drug development targeting deafness- associated potassium channel KCNQ4”. Using the KCNQ4 c.211delC knock-in mouse we collected all auditory brain stem response (ABR), and otoacoustic radiation (DPOAE). The KCNQ4 c.211delC mice had significant hearing loss compared to wild-type control and heterozygous control mice. Hearing loss began shortly after birth, and the mice were deaf by 2 months old. DPOAE results indicate loss of outer hair cells (OHC). Inner ear cellular composition was examined by confocal microscopy to visualize loss of OHC. The project is currently in manuscript preparation for publication in a peer reviewed journal.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、常染色体優性遺伝形式をとる日本人難聴患者に比較的高頻度に認められるKCNQ4遺伝子変異を導入したモデルマウスを確立するとともに、その聴力を経時的に測定し、また、病理組織の観察を行った。得られた情報は将来的な治療法（遺伝子治療等）を確立するための基盤として有用であると期待される。